Diseases of the Pancreas

Question 1

Glasgow criteria for prognosis in acute pancreatitis

Answer 1

• Age > 55 years
• P O 2 < 8 kPa (60 mmHg)
• White blood cell count > 15 × 10 9 /L
• Albumin < 32 g/L (3.2 g/dL)
• Serum calcium < 2 mmol/L (8 mg/dL) (corrected)
• Glucose > 10 mmol/L (180 mg/dL)
• Urea > 16 mmol/L (45 mg/dL) (after rehydration)
• Alanine aminotransferase > 200 U/L
• Lactate dehydrogenase > 600 U/L

Question 2

Initial assessment that predicts severe pancreatitis

Answer 2

• Clinical impression of severity
• Body mass index > 30 kg/m 2
• Pleural effusion on chest X-ray
• APACHE II score > 8

Question 3

Features that predict severe pancreatitis at 24 hours after admission

Answer 3

• Clinical impression of severity
• APACHE II score > 8
• Glasgow score > 3
• Persisting organ failure, especially if multiple
• CRP > 150 mg/L

Question 4

Features that predict severe pancreatitis at 48 hours after admission

Answer 4

• Clinical impression of severity
• Glasgow score > 3
• CRP > 150 mg/L
• Persisting organ failure for 48 hours
• Multiple or progressive organ failure

Question 5

Pathophysiology of acute pancreatitis

Answer 5

-Autodigestion of pancreatic tissue by the pancreatic enzymes, leading to necrosis

-Pancreatic duct obstruction (common bile duct stones, tumours)
-Reflux of bile or duodenal contents into pancreatic ducts (sphincter of Oddi dysfunction)
-Hyperstimulation of pancreas (alcohol, triglycerides)
-Defective intracellular transport and secretion of pancreatic zymogens

Question 6

Triggers of acute pancreatitis

Answer 6

-Alcohol
-Gallstones
-Pancreatic duct obstruction

Question 7

Common causes of acute pancreatitis

Answer 7

• Gallstones
• Alcohol
• Idiopathic causes
• Post-ERCP (endoscopic retrograde cholangiopancreatography)

Question 8

Rare causes of acute pancreatitis

Answer 8

• Post-surgical (abdominal, cardiopulmonary bypass)
• Trauma
• Drugs (azathioprine/mercaptopurine, thiazide diuretics, sodium valproate)
• Metabolic (hypercalcaemia, hypertriglyceridaemia)
• Pancreas divisum
• Sphincter of Oddi dysfunction
• Infection (mumps, Coxsackie virus)
• Hereditary factors
• Renal failure
• Organ transplantation (kidney, liver)
• Severe hypothermia
• Petrochemical exposure

Question 9

GET SMASHED

Answer 9

Gallstones
Ethanol
Trauma
Steroids
Mumps (other viruses include Coxsackie B)
Autoimmune (e.g. polyarteritis nodosa) Ascaris infection
Scorpion venom
Hypertriglyceridaemia, Hyperchylomicronaemia, Hypercalcaemia, Hypothermia
ERCP
Drugs (azathioprine, mesalazine*, didanosine, bendroflumethiazide, furosemide, pentamidine, steroids, sodium valproate)

Question 10

Clinical features of acute pancreatitis

Answer 10

-Severe, constant upper epigastric pain, of increasing intensity over 15–60 minutes, which radiates to the back.
-Nausea and vomiting are common.
-Marked epigastric tenderness, but in the early stages, guarding and rebound tenderness are absent because the inflammation is principally retroperitoneal.
-Bowel sounds become quiet or absent as paralytic ileus develops.
-In severe cases, the patient becomes hypoxic and develops hypovolaemic shock with oliguria.
-Discoloration of the flanks (Grey Turner’s sign) or the periumbilical region (Cullen’s sign) is a feature of severe pancreatitis with haemorrhage.
-Low grade fever

-Rarely, ischaemic Purtscher retinopathy: temporary or permanent blindness

Question 11

Differential diagnosis of acute pancreatitis

Answer 11

-Perforated viscus
-Acute cholecystitis
-Myocardial infarction

Question 12

Pancreatic complications of acute pancreatitis

Answer 12

-Necrosis
=Non-viable pancreatic tissue and peripancreatic tissue death; frequently infected

-Pseudocyst
=Disruption of pancreatic ducts
=Walled with granulation or fibrous tissue, 4+ weeks after attack, mostly retrogastric, elevate amylase, CT ERCP MRI USS, observed for 12 weeks as 50% resolve
=Endoscopic or surgical cystogastromy or aspiration

-Pancreatic ascites or pleural effusion
=disruption of pancreatic ducts

-Abscess
=Circumscribed collection of pus close to the pancreas and containing little or no pancreatic necrotic tissue
=Transgastric drainage is one method of treatment, endoscopic drainage is an alternative

-Peripancreatic fluid collections
=25%, lack wall of granulation or fibrous tissue, may resolve or develop into pseudocysts or abscesses, avoid aspiration and drainage

-Haemorrhage
=Infected necrosis may involve vascular structures with resultant haemorrhage that may occur de novo or as a result of surgical necrosectomy.
=When retroperitoneal haemorrhage occurs Grey Turner’s sign may be identified

Question 13

Systemic complications of acute pancreatitis

Answer 13

-Systemic inflammatory response syndrome (SIRS/ ARDS)
=Increased vascular permeability from cytokine, platelet-aggregating factor and kinin release

-Hypoxia
=Acute respiratory distress syndrome (ARDS) due to microthrombi in pulmonary vessels

-Hyperglycaemia
=Disruption of islets of Langerhans with altered insulin/glucagon release

-Hypocalcaemia
=Sequestration of calcium in fat necrosis, fall in ionised calcium

-Reduced serum albumin concentration
=Increased capillary permeability

Question 14

GI complications of acute pancreatitis

Answer 14

-Upper gastrointestinal bleeding
=Gastric or duodenal erosions

-Variceal haemorrhage
=Splenic or portal vein thrombosis

-Erosion into colon
=Erosion by pancreatic pseudocyst

-Duodenal obstruction
=Compression by pancreatic mass

-Obstructive jaundice
=Compression of common bile duct

Question 15

Describe pancreatic pseudocysts

Answer 15

-Pancreatic fluid collection= A collection of fluid and debris may develop in the lesser sac, following inflammatory rupture of the pancreatic duct
-It is initially contained within a poorly defined, fragile wall of granulation tissue, which matures over a 6-week period to form a fibrous capsule.
-Such ‘pseudocysts’ are common and usually asymptomatic, resolving as the pancreatitis recovers.
-Pseudocysts greater than 6 cm in diameter seldom disappear spontaneously and can cause constant abdominal pain and compress or erode surrounding structures, including blood vessels, to form pseudoaneurysms.
-Large pseudocysts can be detected clinically as a palpable abdominal mass.

Question 16

How does pancreatic ascites occur?

Answer 16

-Fluid leaks from a disrupted pancreatic duct into the peritoneal cavity.
-Leakage into the thoracic cavity can result in a pleural effusion or a pleuro-pancreatic fistula.

Question 17

Investigations of acute pancreatitis

Answer 17

-Raised serum amylase (>x3 normal) or lipase useful for late presentations >24 hours) concentrations and ultrasound or CT evidence of pancreatic swelling.
=a diagnosis of acute pancreatits can be made without imaging if characteristic pain + amylase/lipase > 3 times normal level
=however, early ultrasound imaging is important to assess the aetiology as this may affect management - e.g. patients with gallstones/biliary obstruction
=other options include contrast-enhanced CT

-Plain X-rays exclude perforation or obstruction and identify pulmonary complications.
-Amylase concentrations may have returned to normal if measured 24–48 hours after onset
-A persistently elevated serum amylase concentration suggests pseudocyst formation
-Peritoneal amylase concentrations are massively elevated in pancreatic ascites.
-Serum lipase measurements =greater diagnostic accuracy for acute pancreatitis.

-Ultrasound to confirm diagnosis, although in the earlier stages the gland may not be grossly swollen.

-Contrast-enhanced pancreatic CT performed 6–10 days after admission can be useful in assessing viability of the pancreas if persisting organ failure, sepsis or clinical deterioration is present (pancreatic necrosis)
=Decreased pancreatic enhancement
=Gas suggests infection and impending abscess formation, in which case percutaneous aspiration of material for bacterial culture should be carried out and appropriate antibiotics prescribed

Question 18

Management of acute pancreatitis

Answer 18

-Fluid resuscitation
=Aggressive early hydration with crystalloids. In severe cases 3-6 litres of third space fluid loss may occur
=Aim for a urine output of > 0.5mls/kg/hr
=May also help relieve pain by reducing lactic acidosis

-Analgesia
=Pain may be severe so this is a key priority of care
=Intravenous opioids are normally required to adequately control the pain

-Nutrition
=Patients should not routinely be made ‘nil-by-mouth’ unless there is a clear reason e.g. the patient is vomiting
=Enteral nutrition should be offered to anyone with moderately severe or severe acute pancreatitis within 72 hours of presentation
=Parental nutrition should only be used if enteral nutrition has failed or is contraindicated

-Role of antibiotics
=NICE state the following: ‘Do not offer prophylactic antimicrobials to people with acute pancreatitis’
=Potential indications include infected pancreatic necrosis

-Role of surgery
=Patients with acute pancreatitis due to gallstones should undergo early cholecystectomy
=Patients with obstructed biliary system due to stones should undergo early ERCP
=Patients who fail to settle with necrosis and have worsening organ dysfunction may require debridement, fine needle aspiration is still used by some
=Patients with infected necrosis should undergo either radiological drainage or surgical necrosectomy. The choice of procedure depends upon local expertise

Question 19

Management in ITU for acute pancreatitis

Answer 19

-Opiate analgesics
-Hypovolaemia corrected using normal saline/ other crystalloids.
-Central venous line and urinary catheter= monitor patients with shock.
-Oxygen for hypoxic patients,
-SIRS= ventilatory support
-Hyperglycaemia corrected using insulin
-Hypocalcaemia by intravenous calcium injection.
-Nasogastric aspiration= paralytic ileus
-Enteral feeding in severely catabolic state
=Decreases endotoxaemia and reduce systemic complications.
-Prophylaxis of thromboembolism with subcutaneous low-molecular-weight heparin
-Infected necrosis is treated with antibiotics that penetrate necrotic tissue

Question 20

Management of patients who present with cholangitis or jaundice (in association with severe acute pancreatitis)

Answer 20

-Urgent ERCP to diagnose and treat choledocholithiasis.
-Biliary imaging (using MRCP or EUS) can be carried out after the acute phase has resolved.
-If LFTs return to normal and ultrasound has not demonstrated a dilated biliary tree, laparoscopic cholecystectomy
-Cholecystectomy should be undertaken within 2 weeks of resolution of pancreatitis
-Patients with infected pancreatic necrosis or pancreatic abscess require urgent endoscopic drainage or minimally invasive retroperitoneal pancreatic (MIRP) necrosectomy to debride all cavities of necrotic material.
-Pancreatic pseudocysts can be treated by drainage into the stomach or duodenum.

Question 21

Describe chronic pancreatitis

Answer 21

-Chronic inflammatory disease char­acterised by
=fibrosis
=destruction of exocrine pancreatic tissue.
-Diabetes mellitus occurs in advanced cases because the islets of Langerhans are involved

Question 22

Causes of chronic pancreatitis- TIGARO

Answer 22

-Toxic-metabolic
-Idiopathic (tropical/ early-late onset
-Genetic (CF, haemochromatosis)
-Autoimmune
-Recurrent and severe acute pancreatitis (post-necrotic)
-Obstructive (ductal, tumours, stones, structural)

Around 80% of cases are due to alcohol excess with up to 20% of cases being unexplained.

Question 23

Toxic-metabolic causes of chronic pancreatitis

Answer 23

-Alcohol
-Tobacco
-Hypercalcaemia
-CKD

Question 24

Genetic causes of chronic pancreatitis

Answer 24

-Hereditary pancreatitis (cationic trypsinogen mutation)
-SPINK-1 mutation
-Cystic fibrosis

Question 25

Obstructive causes of chronic pancreatitis

Answer 25

-Ductal adenocarcinoma
-Intraductal papillary mucinous neoplasia
-Pancreas dividum
-Sphincter of Oddi stenosis

Question 26

Mechanisms of chronic pancreatitis

Answer 26

-Oxidative stress
-Toxic-metabolic
-Necrosis-fibrosis
-Recurrent acute pancreatitis
-Duct obstruction

Question 27

Clinical features of chronic pancreatitis

Answer 27

-Middle-aged alcoholic men
-Almost all present with abdominal pain.
-In 50%, this occurs as episodes of ‘acute pancreatitis’
-Relentless, slowly progressive chronic pain without acute exacerbations affects 35% of patients, while the remainder have no pain but present with diarrhoea.
-Pain is due to a combination of increased pressure within the pancreatic ducts and direct involvement of peripancreatic nerves by the inflammatory process.
=Relieved by leaning forwards or by drinking alcohol, worse 15-30 minutes after meal
-Weight loss is common and results from a combination of anorexia, avoidance of food because of post-prandial pain, malabsorption and/or diabetes.
=Steatorrhoea occurs when more than 90% of the exocrine tissue has been destroyed; protein malabsorption develops only in the most advanced cases. 5-25 years after pain onset
-Overall, 30% of patients have (secondary) diabetes but this figure rises to 70% in those with chronic calcific pancreatitis. 20 years later

-Physical examination reveals a thin, malnourished patient with epigastric tenderness.
=Skin pigmentation over the abdomen and back is common and results from chronic use of a hot water bottle (erythema ab igne).
=Many patients have features of other alcohol- and smoking-related diseases.

Question 28

Complications of chronic pancreatitis

Answer 28

• Pseudocysts and pancreatic ascites, which occur in both acute and chronic pancreatitis
• Obstructive jaundice due to benign stricture of the common bile duct as it passes through the diseased pancreas
• Duodenal stenosis
• Portal or splenic vein thrombosis leading to segmental portal hypertension and gastric varices
• Peptic ulcer

Question 29

Investigations of chronic pancreatitis

Answer 29

-Tests to establish the diagnosis
• Ultrasound
• Computed tomography (may show atrophy, calcification or ductal dilatation)
• Abdominal X-ray (may show calcification)
• Magnetic resonance cholangiopancreatography
• Endoscopic ultrasound

-Tests to define pancreatic function
• Collection of pure pancreatic juice after secretin injection (gold standard but invasive and seldom used)
• Pancreolauryl test
• Faecal pancreatic elastase

-Tests to demonstrate anatomy prior to surgery
• Magnetic resonance cholangiopancreatography

Question 30

Intervention in chronic pancreatitis

Answer 30

-Endoscopic therapy
• Dilatation or stenting of pancreatic duct strictures
• Removal of calculi (mechanical or shock-wave lithotripsy)
• Drainage of pseudocysts

-Surgical methods
• Partial pancreatic resection, preserving the duodenum
• Pancreatico-jejunostomy

Question 31

Management of chronic pancreatitis

Answer 31

-Alcohol misuse= avoidance
-Pain relief
=NSAIDs
=Opiates
=Pregabalin and tricyclic antidepressants at low dose
=Oral pancreatic enzyme supplements suppress pancreatic secretion- reduces analgesic consumption
-Malabsorption
=Dietary fat restriction (with supplementary medium-chain triglyceride therapy in malnourished patients)
=PPI optimised duodenal pH for pancreatic enzyme activity

Question 32

Describe autoimmune pancreatitis

Answer 32

-Form of chronic pancreatitis that can mimic cancer, but which responds to glucocorticoids.
-Characterised by abdominal pain, weight loss or obstructive jaundice, without acute attacks of pancreatitis.
-Increased serum IgG or IgG4 and the presence of other autoantibodies.
-Imaging= diffusely enlarged pancreas, narrowing of the pancreatic duct and stricturing of the lower bile duct.
-AIP may occur alone or with other autoimmune disorders, such as Sjögren’s syndrome, primary sclerosing cholangitis or IBD.
-The response to glucocorticoids is usually excellent but some patients require azathioprine.

Question 33

Describe adenocarcinomas of the pancreas

Answer 33

-80/90% pancreatic neoplasms arising from pancreatic duct, typically at the head of the pancreas
-Involve local structures and metastasise to regional lymph nodes
-Advanced disease at time of presentation non-specific presentation
-Men x2
-Associated with increasing age, smoking, chronic pancreatitis
-5-10% patients’ genetic predisposition
-Survival 3-5%
-6-10 months locally advanced disease, 3-5 months with metastases

Question 34

Genetic predisposition to adenocarcinoma of the pancreas

Answer 34

-Hereditary pancreatitis
-HNPCC
-Familial atypical mole multiple melanoma syndrome (FAMMM)

Question 35

Associations with pancreatic cancer

Answer 35

-Increasing age
-Smoking
-Diabetes
-Chronic pancreatitis (alcohol does not appear an independent risk factor though)
-Hereditary non-polyposis colorectal carcinoma
-Multiple endocrine neoplasia
-BRCA2 gene
-KRAS gene mutation

Question 36

Neuro-endocrine tumour of pancreas

Answer 36

-Grow more slowly
-Better prognosis

Question 37

Clinical features of adenocarcinoma of pancreas

Answer 37

-Asymptomatic until advanced stage
=Central epigastric abdominal pain (invasion of coeliac plexus, incessant and gnawing, radiates from upper abdomen to back, eased by bending forward)
=Weight loss, anorexia
=Obstructive painless jaundice (involvement of common bile duct, with severe pruritus)- pale stools, dark urine, pruritis, cholestatic LFT

-Some diarrhoea, vomiting from duodenal obstruction, DM, recurrent venous thrombosis, acute pancreatitis or depression
=Trousseau sign (migratory thrombophlebitis)
=Steatorrhoea (loss of exocrine function)
=DM (loss of endocrine)
=Atypical back pain

-Physical Examination
=Weight loss
=Abdominal mass due to tumour itself (hepatomegaly from mets, palpable gallbladder, epigastric mass)
=Courvoisier’s sign: palpable gallbladder in jaundice consequence of distal biliary obstruction by a pancreatic cancer

Question 38

Investigations of adenocarcinoma of the pancreas

Answer 38

-Ultrasound and contrast-enhanced high resolution CT first line is diagnosis suspected
=Double duct sign (dilation)
-EUS/laparoscopy with ultrasound defines tumour size, involvement of blood vessels and metastatic spread
-MRCP, ERCP (relieve obstructive jaundice)

Question 39

Management of adenocarcinoma of the pancreas

Answer 39

-Surgical resection= 5-year survival 12%: Whipples (results in dumping syndrome, peptic ulcer disease)
-Improved survival with adjuvant chemotherapy using gemcitabine
-ERCP with stenting for palliation
-Only 10-15% resectable as locally advanced
-Palliative
=Analgesics/ coeliac plexus neurolysis

Question 40

Incidental pancreatic masses

Answer 40

-Cystic neoplasms
=rarely malignant and do not require surgery
=Mucinous cysts more in women usually in pancreatic tail
=Aspiration, measuring CEA and amylase concentrations determine mucinous or not
-Mucinous lesions resected

-Intraductal papillary mucinous neoplasia (IPMN)
=elderly men
=main pancreatic duct with marked dilation and plugs of mucous
=pre-malignant but indolent condition